Use Of Clarithromycin Research Articles

Adverse events with quetiapine and clarithromycin coprescription: A population-based retrospective cohort study.

Quetiapine is an atypical antipsychotic predominantly metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. We studied the risk of adverse events following coprescription of clarithromycin (a strong CYP3A4 inhibitor) versus azithromycin (not a CYP3A4 inhibitor) in quetiapine users. This was a population-based retrospective cohort study from 2004 to 2020 in Ontario, Canada in adult quetiapine users newly co-prescribed clarithromycin (n = 16,909) or azithromycin (n = 25,267). The primary outcome was the composite of hospital encounters with encephalopathy (defined as a diagnosis of delirium, disorientation, transient alteration of awareness, transient ischemic attack, or unspecified dementia), a fall, or a fracture within 30 days of new coprescription. Secondary outcomes were individual components of the composite outcome, hospital encounter with computed tomography(CT) head scan, and all-cause mortality. Coprescription of clarithromycin versus azithromycin with quetiapine was associated with a higher risk of the primary composite outcome (365 of 16,909 clarithromycin users [2.2%] vs. 309 of 16,929 azithromycin users [1.8%]; absolute risk increase, 0.34% [95% confidence interval,CI, 0.04-0.63]; relative risk [RR], 1.19 [95% CI,1.02-1.38]). This was primarily driven by an increase in fragility fractures (78 of 16,909 clarithromycin users [0.5%] vs. 45 of 16,923 azithromycin users [0.3%]; absolute risk increase, 0.20% [95% CI, 0.07-0.32]; RR, 1.74 [95% CI, 1.21-2.52]). Hospital encounters with a CT head scan were higher in clarithromycin users (220 of 16,909 [1.3%] vs. 175 of 16,923 azithromycin users [1.0%]; absolute risk increase, 0.27% [95% CI, 0.04-0.50]; RR, 1.26 [95% CI, 1.04-1.54]), but there was no difference in hospital encounters with encephalopathy, falls, or all-cause mortality between macrolide groups. Among adults taking quetiapine, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically greater 30-day risk of a hospital encounter for encephalopathy, falls, or fracture, which was predominantly related to a higher rate of fragility fractures.

Determination of Helicobacter pylori resistance to clarithromycin in biopsy samples of gastric mucosa using TaqMan® MGB probes

Objective. To study primary resistance of H. pylori to clarithromycin in residents of Gomel region by real-time polymerase chain reaction (PCR RT) using TaqMan® MGB probes.Materials and methods. The study included 184 patients diagnosed with gastritis and duodenitis, K29, median age 48.5 years (25% and 75% were 37 and 61 years old). According to the patients’ questionnaires, no clarithromycin-based eradication therapy was administered. To determine the resistance of H. pylori to clarithromycin, a PCR RV method using TagMan® MGB probes was used.Results. All 184 tested DNA samples were positive for the Rnase P gene (ICS) and were considered in further analysis (Ct, HEX 20.20-34.14). DNA from the cagH gene (Ct, FAM 21.26-33.04), indicating infection with the bacterium, was confirmed in 152 samples (82.6%). DNA from the 23SrRNA gene (point mutations A2142G and A2143G) was detected in 16 of 152 DNA samples 10.5 % (Ct, Hex 20.24-31.17). The positive control samples had characteristic curve growth in the corresponding detection channels; no curve growth was observed in the negative samples.Conclusion. The primary resistance of H. pylori to clarithromycin in the residents of Gomel region was 10.5%, and the use of triple first-line eradication therapy, including PPIs, amoxicillin and clarithromycin, as empirical in this region is consistent with the Maastricht III-VI recommendations and Decree of the Ministry of Health of the Republic of Belarus of 01.06.2017 № 54: clinical protocol “Diagnosis and treatment of patients with digestive diseases.” The use of PCR RT using TaqMan® MGB probes is justified to determine the resistance of H. pylori to clarithromycin, to prescribe individualized treatment and to evaluate the effectiveness of eradication regimens.

Side Effects - What Do We Actually Know About Them?

In a world, there are many diseases, which spread faster, than we can imagine. By coughing just once - 20 000 viruses are spread – some of which rocket out at speeds greater than 322 km per hour and might last in the air for hours. [1] Over 95% of the world’s inhabitants have health issues, with over a third having more than five disorders. [2] It is not always enough to have natural healing to get well. The help usually is treatment with pills, which are supposed to help, and cure the patient in the very best cases. However, what do we know about consequences of such treatment? I, the doctor, who believes in evidence based medicine, daily face cases, that request to be questioned about. This is the case report of two patients, looked at through the prism of side effects and morbidity - the first case contain visual perception disturbances after the use of clarithromycin, the second- hair loss after the use of atorvastatin. And the third case, involving multidisciplinary approach to an epileptic seizures and truck driving.

Unveiling the Differential Impact of Clarithromycin and Metronidazole on the Incretin Effect of Sitagliptin

Background: Sitagliptin is a commonly used drug for the treatment of type 2 diabetes. Studies show that diabetic patients are at high risk of suffering severe complications after amoebic infection. To treat these amoebic infections drugs like clarithromycin and metronidazole are most commonly indicated. Methods: Studies were conducted in normal male Wistar rats with oral doses of 10 mg/kg body weight of sitagliptin, 10 mg/kg body weight of clarithromycin & 5 mg/kg body weight of metronidazole, and their combination for duration of 14 days. Blood glucose level was analyzed on weekly basis with the help of a glucometer. For measuring plasma insulin the blood was collected with heart puncture and analyzed with the help of ELISA. Result: The clarithromycin and metronidazole themselves do not have any hypoglycemic.However, when clarithromycin is used together with sitagliptin, it increases the anti-diabetic effect of sitagliptin. This means that there is drug-drug interaction between clarithromycin and sitagliptin. After evaluation of liver drug-metabolizing enzyme, it was concluded that clarithromycin inhibits the CYP3A4 enzyme which is responsible for the metabolism of sitagliptin. As a result the anti-diabetic effect of sitagliptin increases. However, together use of metronidazole and sitagliptin do not have such type of drug interactions. Conclusion: From this study it was concluded that the combined use of clarithromycin and sitagliptin may need a little dose adjustment and care should be taken when the combination is prescribed to the patient. While the combination use of metronidazole with sitagliptin has no significant effect on sitagliptin therapy.

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease

BackgroundClarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD).MethodsThis nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD–PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed.ResultsClarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93–1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57–1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89–1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant.ConclusionConcerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

0797 Reclaiming Her Life: Successful Treatment of Kleine-Levin Syndrome with Transdermal Flumazenil

Abstract Introduction Kleine-Levin Syndrome (KLS) is a rare disorder of hypersomnolence with cognitive and behavioral disturbances. Currently, there are no definitive treatment recommendations although stimulants, mood stabilizers, and even electroconvulsive therapy have been utilized with inconsistent results. Report of Cases: A 23-year-old female with a history of depression, anxiety, obsessive-compulsive disorder, Hashimoto's thyroiditis, lupus, and morbid obesity presented to our facility for management of debilitating episodes of sleepiness due to KLS, diagnosed at the age of 22. She reported good health until a series of viral illnesses at the age of 20. She then began experiencing sleep episodes requiring 20-22 hours of sleep per day, only awakening to eat and use the bathroom. These episodes typically lasted for two weeks and were preceded by periods of hyperphagia and hypersexuality. When she presented to our facility, she was using lithium and modafinil daily along with amantadine and clarithromycin twice daily as needed for episodes of sleepiness. At her initial visit, she was prescribed transdermal flumazenil, a GABA-A receptor/benzodiazepine antagonist, to be used as needed to supplement amantadine and clarithromycin. She was initially requiring flumazenil every other month. After seven months of flumazenil use, the frequency of episodes decreased to every 3-4 months. She would administer two clicks of flumazenil cream on each forearm with the prodrome symptom of fogginess, which would abort the episode. Rarely, she required a second dose 12 hours later. With flumazenil and avoidance of triggers, such as alcohol and sleep deprivation, she reported completing her master’s degree and finally maintaining a job. Ultimately, she discontinued lithium, modafinil, amantadine, and clarithromycin use without reoccurrence of her symptoms. Conclusion This case demonstrates successful treatment of KLS with the use of a GABA-A receptor/benzodiazepine antagonist, flumazenil. Reduction in episodes of sleepiness with flumazenil ultimately led to discontinuing stimulant, mood stabilizer, and clarithromycin use. Early trials of transdermal flumazenil and continued research regarding the use of this medication for patients with KLS may prove to be a promising intervention. Support (If Any) None.

Beneficial ex vivo immunomodulatory and clinical effects of clarithromycin in COVID-19

IntroductionMacrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored. MethodsWe investigated the effect of antibiotics (amoxicillin, azithromycin, clarithromycin, and combined amoxicillin with clarithromycin) on lymphocyte intracellular cytokine levels and monocyte phagocytosis in healthy volunteer PBMCs stimulated ex vivo with SARS-CoV-2 S1+2 spike protein. A retrospective cohort study was performed on intensive care COVID-19 patients. ResultsCo-incubation of clarithromycin with spike protein-stimulated healthy volunteer PBMCs ex vivo resulted in an increase in CD8+ (p = 0.004) and CD4+ (p = 0.007) IL-2, with a decrease in CD8+ (p = 0.032) and CD4+ (p = 0.007) IL-10. The addition of amoxicillin to clarithromycin resulted in an increase in CD8+ IL-6 (p = 0.010), decrease in CD8+ (p = 0.014) and CD4+ (p = 0.022) TNF-alpha, and decrease in CD8+ IFN-alpha (p = 0.038). Amoxicillin alone had no effect on CD4+ or CD8+ cytokines. Co-incubation of azithromycin resulted in increased CD8+ (p = 0.007) and CD4+ (p = 0.011) IL-2. There were no effects on monocyte phagocytosis. 102 COVID-19 ICU patients received antibiotics on hospital admission; 62 (61%) received clarithromycin. Clarithromycin use was associated with reduction in mortality on univariate analysis (p = 0.023), but not following adjustment for confounders (HR = 0.540; p = 0.076). ConclusionsClarithromycin has immunomodulatory properties over and above azithromycin. Amoxicillin in addition to clarithromycin is associated with synergistic ex vivo immunomodulatory properties. The potential benefit of clarithromycin in critically ill patients with COVID-19 and other viral pneumonitis merits further exploration.

Diagnosis and Treatment of Helicobacter pylori Infection.

The last 5 years have seen major shifts in defining whom to test and how to treat Helicobacter pylori infection. Peptic ulcer has changed from a chronic disease to a one-off condition, and countries with a high incidence of gastric cancer have begun implementing population-wide screening and treatment. A proactive approach to testing and treatment of H. pylori is now recommended, including outreach to family members of individuals diagnosed with active infection as well as high-risk local populations such as immigrants from high-risk countries. Increasing antimicrobial resistance has resulted in an overall decline in treatment success, causing a rethinking of the approach to development of treatment guidelines as well as the need to adopt the principles of antibiotic usage and antimicrobial stewardship. Required changes include abandoning empiric use of clarithromycin, metronidazole, and levofloxacin triple therapies. Here, we discuss these transformations and give guidance regarding testing and use of therapies that are effective when given empirically.

Síndrome torácica aguda em paciente escolar com doença falciforme: um relato de caso

OBJECTIVE: To describe the case of a male pediatric patient with acute thoracic syndrome (ATS) in sickle cell anemia, linking it to the medical literature. CASE DESCRIPTION: A 9-year-old male patient, developed strong pain associated to headache and priapism, hence admitted to the emergency of a tertiary referral hospital. A priapism relief was noticed after hydration and morphine sedation. He developed severe acute thoracic syndrome, pneumonia and pleural effusion. The use of cefotaxime, clindamycin and clarithromycin was started. Mechanical ventilation was necessary and the patient was sent to the intensive care unit. On the tenth day, patient developed sepsis consequently cefotaxime and clindamycin were interrupted and piperacilin + tazobactam + linezoline were introduced. Kept clarithromycin. On the twelfth day, he had prophylaxis for pulmonary thromboembolism (TEP) with enoxaparin due to the expanded D-dimer. A second TEP was confirmed after some days. Three blood transfusions were needed during the hospitalization. He recovered gradually and was discharged on the thirty-sixth day keeping on thromboembolism prophylaxis until his return for other tests. COMMENTS: Patient had the infection and pulmonary thromboembolism as possible causes to trigger the acute thoracic syndrome. As observed in the medical literature, the pain crises anticipated the ATS. Alterations were observed on the laboratorial tests and imaging exams compatible with cases described by other authors. The good progress was the reflex from the adequate diagnosis and treatment.

Correlation between clarithromycin resistance, virulence factors and clinical characteristics of the disease in Helicobacter pylori infected patients in Shahrekord, Southwest Iran

The purpose of this study was to determine the mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from biopsy samples that were collected from the endoscopic ward of Shahrekord Hajar teaching Hospital and also to study the frequency of virulence factor and their correlation and pathological findings with clarithromycin resistance during the years 2019–2020. In this cross-sectional descriptive study, 152 patients with Helicobacter pylori infection were considered, and then, two common A2142G and A2143G mutations in the 23SrRNA gene associated with resistance were analyzed by Real-time PCR (Taq man). The presence of vacA, iceA1, iceA2, cagA, babA2, and oipA virulence genes was investigated by PCR and electrophoresis in 8% polyacrylamide gel. Then, data were analyzed using the relevant statistical tests. In this study, the frequency of Helicobacter pylori was 76% and the frequency of mutant isolates was 57.2%. The frequencies of A2142G and A2143G point mutations were 42.1% and 28.3%. There was a significant correlation among oipA, vacA, and iceA1 virulence factors, type of disease, chronic inflammatory score, and glandular atrophy with the antibiotic resistance to clarithromycin. There was no significant correlation between the age and sex of the patients with antibiotic resistance. According to the results of this study, it seems that the use of clarithromycin to combat this bacterium should be limited.

Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial.

IntroductionThe anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19.MethodsAn open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed.ResultsThe primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1–92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported.ConclusionsEarly clarithromycin treatment provides most of the clinical improvement in moderate COVID-19.Trial RegistrationClinicalTrials.gov, NCT04398004Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00505-8.

A Relapsing Case of Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially fatal adverse hypersensitivity reaction often secondary to therapeutic medications. There is a wide variation in the incidence of the disease and is dependent on the genetic makeup of the individual. The most common presentation includes skin eruptions, fever, generalized lymphadenopathy, eosinophilia, and internal organ involvement (most commonly, liver, kidneys, and lungs). Some less common features are dysphagia, agranulocytosis, and chylous ascites. The most common drugs causing DRESS syndrome include carbamazepine, allopurinol, sulfasalazine, phenobarbital, and lamotrigine. Differential diagnosis has Steven-Johnson Syndrome/Toxic Epidermal Necrolysis, hypereosinophilic syndrome, and Sezary syndrome. Systemic corticosteroids are the first-line treatment for DRESS syndrome and the withdrawal of the offending agent and supportive therapy. We report a rare case of DRESS syndrome following the use of clarithromycin and moxifloxacin, where rapid steroid taper resulted in relapse.

Teratogenic effect of clarithromycin on rabbit,s foeti

Objective: To evaluate the teratogenic effects of clarithromycin on developing rabbit.Design: Randomized controlled study.Animals: Twenty one female New Zealand rabbits. Procedure: The pregnant female rabbits (21) were allocated into 4 groups. Control group (G1) (6 rabbits) received placebo. Other groups received clarithromycin (at a dose of 30 mg/kg b.wt orally) for ten days during the first stage (group2, n=6), the second stage (group3, n=6) or the third stage (group 4, n=3) of pregnancy. Three rabbits from each group were slaughtered on 20th and 30th days of pregnancy. Teratogenic effects were evaluated morphologically and histopathologically. Results: The therapeutic dose of clarithromycin exhibited morphological malformations, significant decrease (P≤0.05) in viable foeti mean, the mean values of the body weight and the fetal crown-rump length. However there was significant increase (P≤0.05) in dead foeti, fetal resorption rate, pre and post-implantation death in different stages of pregnancy. Visceral fetal abnormalities revealed dilatation of lateral ventricles of brain, thickening of the ventricular wall of the heart, and slight unilateral or bilateral widening of the renal pelvis. Skeleton fetal malformations showed incomplete ossification of 5th sternipri with absence of last ribs. Histopathological examination confirm teratogenic effects of clarithromycin. Conclusion and clinical relevance: The use of clarithromycin during pregnancy should be prohibited.

Increased risk of short-term depressive disorder after Helicobacter pylori eradication: A population-based nested cohort study.

Depressive disorder is a major psychiatric illness, and a disturbed brain-gut-microbiome axis may contribute to its pathophysiology. Chronic Helicobacter pylori (H.pylori) infections are common in the general population and using multiple antibiotics is required for its eradication, which is associated with gut dysbiosis and may lead to depression. We aimed to evaluate the risk of psychiatrist-diagnosed depression in patients with peptic ulcer diseases (PUD) receiving anti-H.pylori therapy. We collected data from the National Health Insurance Research Database (NHIRD) in Taiwan on PUD patients undergoing antibiotic treatment for H.pylori infection; patients and controls were matched for age, sex, income, level of urbanization, and comorbidities. Of the 1million beneficiaries in the NHIRD, we identified 7087 patients for inclusion in the eradication cohort and 7087matched non-eradication controls with PUD. Antibiotic therapy is associated with a short-term (<30days) increase in the incidence of psychiatrist-diagnosed depressive disorder (p=0.009, after multiple comparisons with Bonferroni correction) in the eradication cohort compared with the controls. Female (OR: 4.55, 95% CI: 1.53-13.48) PUD patients were more likely to display an increased risk of depression within 30days after eradication therapy. Clarithromycin use was related to an elevated likelihood (OR: 3.14, 95% CI: 1.45-6.80) of subsequent depressive disorder within 30days after eradication therapy. Antibiotic eradication treatment for H.pylori infection is associated with a significant short-term (less than 30days) increase in the incidence of psychiatrist-diagnosed depressive disorder, which can be overlooked by gastroenterologists and general practitioners.

Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea: 2020 Revised Edition

Helicobacter pylori (H. pylori) infection is one of the most common infectious diseases worldwide. Although its incidence is gradually decreasing, about half of the world's population still get infected. H. pylori infection is responsible for substantial gastrointestinal morbidity worldwide. It is the most common cause of gastric and duodenal ulcers as well as gastric cancer. Since the revision of the H. pylori Clinical Practice Guidelines in 2013, the eradication rate of H. pylori has gradually decreased with the use of classical triple therapy, wherein amoxicillin, clarithromycin, and proton pump inhibitors are administered, for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was due to increased antimicrobial resistance induced by the use of antibiotics, especially clarithromycin. The update of clinical practice guideline for treatment of H. pylori was developed based on evidence-based medicine by conducting a meta-analysis. The draft recommendations were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines are designed to provide patients, nurses, medical school students, policymakers, and clinicians with clinical evidence to guide primary care and treatment of H. pylori infection. These may differ from current medical insurance standards and will be revised further, if necessary, based on research-based evidence.

Clarithromycin use for adjunct surgical prophylaxis before non-elective cesarean deliveries to adapt to azithromycin shortages in COVID-19 pandemic.

ObjectiveThis study aimed to evaluate safety and effectiveness of clarithromycin as adjunctive antibiotic prophylaxis for patients undergoing non-elective cesarean delivery in comparison with no macrolides, to adapt to azithromycin shortages in COVID-19 pandemic.Study designWe conducted a multi-center, prospective observational cohort study from March 23, 2020 through June 1, 2020. We followed all women receiving either clarithromycin or no macrolide antibiotic for adjunct surgical prophylaxis for non-elective cesarean deliveries. The primary outcome was development of postpartum endometritis. Secondary outcomes included meconium-stained amniotic fluid at time of cesarean delivery, neonatal sepsis, neonatal intensive care unit admission, and neonatal acute respiratory distress syndrome. All patients in this study were tested for SARS-CoV-2 infection and resulted negative.ResultsThis study included 240 patients, with 133 patients receiving clarithromycin and 107 patients receiving no adjunct macrolide prophylaxis. Patients receiving clarithromycin were noted to have significantly lower rates of postpartum endometritis as compared to those who did not receive adjunct prophylaxis (4.5% versus 11.2%, p = 0.025). In crude (unadjusted) analysis, a significantly lower risk of developing endometritis was noted in the clarithromycin group as compared to the control group (66% decreased risk, 95% CI 0.12 to 0.95, p = 0.040). When adjusted for perceived confounders, a significant difference was again noted (67% decreased risk, 95% CI 0.11 to 0.97, p = 0.034). Stratified analysis of significantly different demographic factors including Black race, BMI, and age was performed. A significantly decreased risk of development of endometritis when taking clarithromycin versus no adjunct macrolide was noted for Black race women in crude and adjusted models (crude: 87% decreased risk, 95% CI 0.08 to 0.83, p = 0.032; adjusted: 91% decreased risk, 95% CI 0.06 to 0.79, p = 0.026). This was also noted for women aged 18–29 years in crude and adjusted models (crude: model, 79% decreased risk, 95% CI 0.06 to 0.80, p = 0.014; adjusted model: 75% decreased risk, 95% CI 0.06 to 0.94, p = 0.028). All other stratified analyses did not yield significant differences in endometritis risk.ConclusionOur study suggests that administration of clarithromycin for adjunctive surgical prophylaxis for non-elective cesarean deliveries may be a safe option that may provide suitable endometritis prophylaxis in cases where azithromycin is unavailable, as was the case during the start of COVID-19 pandemic, most especially for Black race women and women ages 18–29 years.

Genetic and pharmacological relationship between P-glycoprotein and increased cardiovascular risk associated with clarithromycin prescription: An epidemiological and genomic population-based cohort study in Scotland, UK.

There are conflicting reports regarding the association of the macrolide antibiotic clarithromycin with cardiovascular (CV) events. A possible explanation may be that this risk is partly mediated through drug-drug interactions and only evident in at-risk populations. To the best of our knowledge, no studies have examined whether this association might be mediated via P-glycoprotein (P-gp), a major pathway for clarithromycin metabolism. The aim of this study was to examine CV risk following prescription of clarithromycin versus amoxicillin and in particular, the association with P-gp, a major pathway for clarithromycin metabolism. We conducted an observational cohort study of patients prescribed clarithromycin or amoxicillin in the community in Tayside, Scotland (population approximately 400,000) between 1 January 2004 and 31 December 2014 and a genomic observational cohort study evaluating genotyped patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study, a longitudinal cohort study of 18,306 individuals with and without type 2 diabetes recruited between 1 December 1988 and 31 December 2015. Two single-nucleotide polymorphisms associated with P-gp activity were evaluated (rs1045642 and rs1128503 -AA genotype associated with lowest P-gp activity). The primary outcome for both analyses was CV hospitalization following prescription of clarithromycin versus amoxicillin at 0-14 days, 15-30 days, and 30 days to 1 year. In the observational cohort study, we calculated hazard ratios (HRs) adjusted for likelihood of receiving clarithromycin using inverse proportion of treatment weighting as a covariate, whereas in the pharmacogenomic study, HRs were adjusted for age, sex, history of myocardial infarction, and history of chronic obstructive pulmonary disease. The observational cohort study included 48,026 individuals with 205,227 discrete antibiotic prescribing episodes (34,074 clarithromycin, mean age 73 years, 42% male; 171,153 amoxicillin, mean age 74 years, 45% male). Clarithromycin use was significantly associated with increased risk of CV hospitalization compared with amoxicillin at both 0-14 days (HR 1.31; 95% CI 1.17-1.46, p < 0.001) and 30 days to 1 year (HR 1.13; 95% CI 1.06-1.19, p < 0.001), with the association at 0-14 days modified by use of P-gp inhibitors or substrates (interaction p-value: 0.029). In the pharmacogenomic study (13,544 individuals with 44,618 discrete prescribing episodes [37,497 amoxicillin, mean age 63 years, 56% male; 7,121 clarithromycin, mean age 66 years, 47% male]), when prescribed clarithromycin, individuals with genetically determined lower P-gp activity had a significantly increased risk of CV hospitalization at 30 days to 1 year compared with heterozygotes or those homozygous for the non-P-gp-lowering allele (rs1045642 AA: HR 1.39, 95% CI 1.20-1.60, p < 0.001, GG/GA: HR 0.99, 95% CI 0.89-1.10, p = 0.85, interaction p-value < 0.001 and rs1128503 AA 1.41, 95% CI 1.18-1.70, p < 0.001, GG/GA: HR 1.04, 95% CI 0.95-1.14, p = 0.43, interaction p-value < 0.001). The main limitation of our study is its observational nature, meaning that we are unable to definitively determine causality. In this study, we observed that the increased risk of CV events with clarithromycin compared with amoxicillin was associated with an interaction with P-glycoprotein.

Evidence-based Guidelines for the Treatment of Helicobacter pylori Infection in Korea: 2020 Revised Edition

Helicobacter pylori (H. pylori) infection is one of the most common infectious diseases worldwide. Although its incidence is gradually decreasing, about half of the world's population still get infected. H. pylori infection is responsible for substantial gastrointestinal morbidity worldwide. It is the most common cause of gastric and duodenal ulcers as well as gastric cancer. Since the revision of the H. pylori Clinical Practice Guidelines in 2013, the eradication rate of H. pylori has gradually decreased with the use of classical triple therapy, wherein amoxicillin, clarithromycin, and proton pump inhibitors are administered, for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was due to increased antimicrobial resistance induced by the use of antibiotics, especially clarithromycin. The update of clinical practice guideline for treatment of H. pylori was developed based on evidence-based medicine by conducting a meta-analysis. The draft recommendations were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines are designed to provide patients, nurses, medical school students, policymakers, and clinicians with clinical evidence to guide primary care and treatment of H. pylori infection. These may differ from current medical insurance standards and will be revised further, if necessary, based on research-based evidence.

Low Adherence to Society Guidelines for the Management of Helicobacter Pylori Among Pediatric Gastroenterologists.

The revised ESPGHAN/NASPGHAN 2016 guideline on the diagnosis and management of Helicobacter pylori (H pylori) infection discourages a "test and treat" strategy. Instead, upper endoscopy (EGD) is recommended when a valid clinical indication is present. Likewise, new treatment recommendations for first-line therapies strongly encourage obtaining antimicrobial susceptibility before treatment. We conducted this study to assess the effect of revised guidelines on clinical practice at our center. Retrospective chart review of patients with H pylori infection diagnosis either by serology, stool antigen test, urea breath test, or EGD at Boston Children's Hospital between January 2013 and July 2019. We compared demographic and clinical data between initial guideline and 2016 revision (January 2013 to November 2016) and period after revised guideline (December 2016 to July 2019). Two hundred and fifty-six patients were included. EGD was the initial diagnostic test in 49% (50/103, prerevised guideline) and in 52% (79/153, postrevised guideline). Biopsy culture was sent in 3% of patients for both periods (3/103 and 4/153, respectively). PPI-clarithromycin-amoxicillin triple therapy was the most common regimen in both periods. Clarithromycin use was lower in postrevised guideline period (P = 0.003) whereas the opposite was noted for metronidazole and tetracycline (P = 0.009 and P = 0.02, respectively). There was no significant difference in eradication rate between periods (86% vs 81%). Low adherence to the updated H pylori guideline recommendations was observed among pediatric gastroenterologists at our center with low use of gastric biopsy culture. The guideline revision was associated with avoidance of clarithromycin use as a second-line therapy, but no change in eradication rates. Future interventions should address the importance of obtaining gastric biopsy culture for antibiotic susceptibilities to guide therapy.

Does Clarithromycin Use in Acute Viral Bronchiolitis Shorten Length of Hospital Stay?

Introduction: Acute bronchiolitis is the most common cause of hospitalization among infants. Although antibiotics are not recommended in the absence of secondary bacterial infection, rates of antibiotic usage is high rate in clinical practices Objectives: To test the hypothesis that clarithromycin use in infants with acute viral bronchiolitis shortens length of hospital stay. Materials and Methods: One hundred sixty-seven patients aged 1-24 months hospitalized for treatment with a diagnosis of acute viral bronchiolitis at pediatric clinic between April 2017 and May 2018 were investigated retrospectively. The patients were divided into two separate groups, Group A (122 patients), using clarithromycin therapy during hospitalization, and Group B (45 patients), which did not receive clarithromycin (Group B). Demographic and clinical data, treatments received, and duration of hospital stay were obtained from patients’ records. Results: The rate of clarithromycin use in this study was 73%. No statistically significant difference in length of hospital stay was determined between patients receiving clarithromycin and those receiving no antibiotic therapy. However, length of hospital stay decreased with age. Clarithromycin use elicited no statistically significant decrease in hospital stay in patients with acute viral bronchiolitis. Conclusions: The routine use of clarithromycin is not recommended in acute viral bronchiolitis in the light of its cost and side-effects, and the fact is has no impact on clinical status and hospital stay